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1.
Lab Invest ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013530

RESUMO

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

2.
Transl Vis Sci Technol ; 11(1): 32, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35061010

RESUMO

Purpose: Corneal chemical injuries (CCI) obscure vision by opacifying the cornea; however, current treatments may not fully restore clarity. Here, we investigated potential-driven electrochemical treatment (P-ECT) to restore clarity after alkaline-based CCI in ex vivo rabbit corneas and examined collagen fiber orientation changes using second harmonic generation (SHG). Methods: NaOH was applied to the corneas of intact New Zealand white rabbit globes. P-ECT was performed on the opacified cornea while optical coherence tomography (OCT) imaging (∼35 frames per second) was simultaneously performed. SHG imaging evaluated collagen fiber structure before NaOH application and after P-ECT. Irrigation with water served as a control. Results: P-ECT restored local optical clarity after NaOH exposure. OCT imaging shows both progression of NaOH injury and the restoration of clarity in real time. Analysis of SHG z-stack images show that collagen fibril orientation is similar between control, NaOH-damaged, and post-P-ECT corneas. NaOH-injured corneas flushed with water (15 minutes) show no restoration of clarity. Conclusions: P-ECT may be a means to correct alkaline CCI. Collagen fibril orientation does not change after NaOH exposure or P-ECT, suggesting that no irreversible matrix level fiber changes occur. Further studies are required to determine the mechanism for corneal clearing and to ascertain the optimal electrical dosimetry parameters and electrode designs. Translational Relevance: Our findings suggest that P-ECT is a potentially effective, low-cost treatment for alkaline CCI.

3.
Stem Cell Res ; 59: 102637, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34959203

RESUMO

Diabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes, and the leading cause of preventable blindness in working-aged people. Here, we generated an induced pluripotent stem (iPS) cell line using blood-derived cells from a patient with DR. Peripheral blood mononuclear cells (PBMCs) were reprogrammed with Sendai virus.

4.
Comput Intell Neurosci ; 2021: 8292535, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567104

RESUMO

In the Panax notoginseng quality intelligent management system, the big roots and fibrous roots cannot be cut automatically because the machine cannot distinguish the taproot, big roots, and fibrous roots of Panax notoginseng, resulting in the automatic cutting mechanism unable to obtain the control trajectory coordinate reference of the tool feed. To solve this problem, this paper proposes a visual optimal network model detection method, which uses the image detection method of marking anchor frames to improve the detection accuracy. A variety of deep learning network models are modified by the TensorFlow framework, and the best training model is optimized by comparing the results of training, testing, and verification data. This model is used to automatically identify the taproots and provide the control trajectory coordinate reference for the actuator that cuts big roots and fibrous roots automatically. The experimental results show that the optimal network model studied in this paper is effective and accurate in identifying the taproots of Panax notoginseng.


Assuntos
Panax notoginseng , Raízes de Plantas , Tecnologia
5.
Comput Methods Programs Biomed ; 210: 106376, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34500140

RESUMO

BACKGROUND AND PURPOSE: As a simple and reliable systematic method to evaluate the early ischemic changes in the blood supply region of the middle cerebral artery of patients with ischemic stroke, the Alberta Stroke Program Early CT score (ASPECTS) can be used for rapid semi-quantitative evaluation of ischemic lesions, which is helpful to select potential candidates for intravenous and intra-arterial therapies, determine the thrombolytic effect and long-term prognosis. This method mainly relies on doctors' visual observation. However, due to different levels of doctor's experience, the poor inter-reader agreement may result in errors in the final ASPECTS. The purpose of this work was to propose an automated semi-quantitative method for the diagnosis of acute ischemic stroke based on non-contrast computed tomography (NCCT), to provide a reference for doctors in the diagnosis and evaluation. METHODS: NCCT data from a total of 90 patients were included for auto-ASPECTS training and testing. After preprocessing CT images, the regions of interest (ROI) for ASPECTS were labeled using atlas-based segmentation. The mean difference, mean ratio and brain density shifts (BDS) of the corresponding regions of the contralateral brain were used as the standard for quantitative analysis. The auto-ASPECTS method was developed and validated to predict early ischemic changes whose performance was evaluated by the agreement (accuracy) of predictions and consensus scores of two observers. RESULTS: A comparison was made among the results on mean difference, mean ratio, BDS and the combination of multiple parameters as the standard. The result of using BDS alone was relatively better than the result of using any other parameter alone or any combination of multiple parameters, and accuracy in the test set was 0.80. In the test set, accuracy with using different BDS thresholds increased by 6.67% compared with using the consistent BDS threshold. After dichotomy of auto-ASPECTS and consensus scores with the threshold of 7, the agreement of them was 83.3% and there was no significant difference between the two distributions (p = 0.344) in McNemar test. CONCLUSIONS: The proposed auto-ASPECTS method for NCCT images can provide useful information for early diagnosis and evaluation of patients with acute ischemic stroke (AIS).


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Alberta , Encéfalo , Isquemia Encefálica/diagnóstico por imagem , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X
6.
Future Oncol ; 17(33): 4571-4582, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34519220

RESUMO

Aims: To determine how consistently Chinese glioblastoma multiforme (GBM) patients were treated according to the Stupp regimen. Patients and methods: The proportion of treatments conforming to the Stupp regimen and reasons for nonconformity were evaluated in 202 newly diagnosed GBM patients. Results: Only 15.8% of GBM patients received treatments compliant with the Stupp regimen. The main deviations were temozolomide dosages >75 mg/m2 (58/120; 48.3%) and treatment durations <42 days (84/120; 70.0%) in the concomitant phase and temozolomide dosages <150 mg/m2 (89/101; 88.1%) in the maintenance phase. Median overall survival (27.09 vs 18.21 months) and progression-free survival (14.27 vs 12.10 months) were longer in patients who received Stupp regimen-compliant treatments. Conclusion: Increased conformity to the Stupp regimen is needed for GBM patients in China.

7.
J Biomed Opt ; 26(8)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34414705

RESUMO

SIGNIFICANCE: The human vocal fold (VF) oscillates in multiple vectors and consists of distinct layers with varying viscoelastic properties that contribute to the mucosal wave. Office-based and operative laryngeal endoscopy are limited to diagnostic evaluation of the VF epithelial surface only and are restricted to axial-plane characterization of the horizontal mucosal wave. As such, understanding of the biomechanics of human VF motion remains limited. AIM: Optical coherence tomography (OCT) is a micrometer-resolution, high-speed endoscopic imaging modality which acquires cross-sectional images of tissue. Our study aimed to leverage OCT technology and develop quantitative methods for analyzing the anatomy and kinematics of in vivo VF motion in the coronal plane. APPROACH: A custom handheld laryngeal stage was used to capture OCT images with 800 A-lines at 250 Hz. Automated image postprocessing and analytical methods were developed. RESULTS: Novel kinematic analysis of in vivo, long-range OCT imaging of the vibrating VF in awake human subjects is reported. Cross-sectional, coronal-plane panoramic videos of the larynx during phonation are presented with three-dimensional videokymographic and space-time velocity analysis of VF motion. CONCLUSIONS: Long-range OCT with automated computational methods allows for cross-sectional dynamic laryngeal imaging and has the potential to broaden our understanding of human VF biomechanics and sound production.


Assuntos
Laringe , Tomografia de Coerência Óptica , Fenômenos Biomecânicos , Humanos , Fonação , Prega Vocal/diagnóstico por imagem
8.
J Transl Med ; 19(1): 372, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461927

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) and lanthionine synthetase C-like 2 (LanCL2) genes locate in the same amplicon, and co-amplification of EGFR and LANCL2 is frequent in glioblastoma. However, the prognostic value of LANCL2 and EGFR co-amplification, and their mRNA and protein expression in glioblastoma remain unclear yet. METHODS: This study analyzed the prognostic values of the copy number variations (CNVs), mRNA and protein expression of LANCL2 and EGFR in 575 glioblastoma patients in TCGA database and 100 glioblastoma patients in tumor banks of the Shenzhen Second People's Hospital and the Sun Yat-sen University Cancer Center. RESULTS: The amplification of LANCL2 or EGFR, and their co-amplification were frequent in glioblastoma of TCGA database and our tumor banks. A significant correlation was found between the CNVs of LANCL2 and EGFR (p < 0.001). CNVs of LANCL2 or EGFR were significantly correlated with IDH1/2 mutation but not MGMT promoter methylation. Multivariate analysis showed that LANCL2 amplification was significantly correlated with reduced overall survival (OS) in younger (< 60 years) glioblastoma patients of TCGA database (p = 0.043, HR = 1.657) and our tumor banks (p = 0.018, HR = 2.199). However, LANCL2 or EGFR amplification, and their co-amplification had no significant impact on OS in older (≥ 60 years) or IDH1/2-wild-type glioblastoma patients. mRNA and protein overexpression of LANCL2 and EGFR was also frequently found in glioblastoma. The mRNA expression rather than the protein expression of LANCL2 and EGFR was positively correlated (p < 0.001). However, mRNA or protein expression of EGFR and LANCL2 was not significantly correlated with OS of glioblastoma patients. The protein expression level of LANCL2, rather than EGFR, was elevated in relapsing glioblastoma, compared with newly diagnosed glioblastoma. In addition, the intracellular localization of LanCL2, not EGFR, was associated with the grade of gliomas. CONCLUSIONS: Taken together, amplification and mRNA overexpression of LANCL2 and EGFR, and their co-amplification and co-expression were frequent in glioblastoma patients. Our findings suggest that amplification of LANCL2 and EGFR were the independent diagnostic biomarkers for glioblastoma patients, and LANCL2 amplification was a significant prognostic factor for OS in younger glioblastoma patients.


Assuntos
Neoplasias Encefálicas , Receptores ErbB/genética , Glioblastoma , Proteínas de Membrana/genética , Proteínas de Ligação a Fosfato/genética , Idoso , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Variações do Número de Cópias de DNA/genética , Receptores ErbB/metabolismo , Glioblastoma/genética , Humanos , Mutação , Recidiva Local de Neoplasia , Prognóstico , RNA Mensageiro/genética
10.
Cancers (Basel) ; 13(14)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34298796

RESUMO

Non-invasive strategies that can identify oral malignant and dysplastic oral potentially-malignant lesions (OPML) are necessary in cancer screening and long-term surveillance. Optical coherence tomography (OCT) can be a rapid, real time and non-invasive imaging method for frequent patient surveillance. Here, we report the validation of a portable, robust OCT device in 232 patients (lesions: 347) in different clinical settings. The device deployed with algorithm-based automated diagnosis, showed efficacy in delineation of oral benign and normal (n = 151), OPML (n = 121), and malignant lesions (n = 75) in community and tertiary care settings. This study showed that OCT images analyzed by automated image processing algorithm could distinguish the dysplastic-OPML and malignant lesions with a sensitivity of 95% and 93%, respectively. Furthermore, we explored the ability of multiple (n = 14) artificial neural network (ANN) based feature extraction techniques for delineation high grade-OPML (moderate/severe dysplasia). The support vector machine (SVM) model built over ANN, delineated high-grade dysplasia with sensitivity of 83%, which in turn, can be employed to triage patients for tertiary care. The study provides evidence towards the utility of the robust and low-cost OCT instrument as a point-of-care device in resource-constrained settings and the potential clinical application of device in screening and surveillance of oral cancer.

11.
BMC Med Imaging ; 21(1): 92, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059015

RESUMO

BACKGROUND: Differential diagnosis of tumour recurrence (TuR) from treatment effects (TrE), mostly induced by radiotherapy and chemotherapy, is still difficult by using conventional computed tomography (CT) or magnetic resonance (MR) imaging. We have investigated the diagnostic performance of PET/CT with 3 tracers, 13N-NH3, 18F-FDOPA, and 18F-FDG, to identify TuR and TrE in glioma patients following treatment. METHODS: Forty-three patients with MR-suspected recurrent glioma were included. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the lesion and the lesion-to-normal grey-matter cortex uptake (L/G) ratio were obtained from each tracer PET/CT. TuR or TrE was determined by histopathology or clinical MR follow-up for at least 6 months. RESULTS: In this cohort, 34 patients were confirmed to have TuR, and 9 patients met the diagnostic standard of TrE. The SUVmax and SUVmean of 13N-NH3 and 18F-FDOPA PET/CT at TuR lesions were significantly higher compared with normal brain tissue (13N-NH3 0.696 ± 0.558, 0.625 ± 0.507 vs 0.486 ± 0.413; 18F-FDOPA 0.455 ± 0.518, 0.415 ± 0.477 vs 0.194 ± 0.203; both P < 0.01), but there was no significant difference in 18F-FDG (6.918 ± 3.190, 6.016 ± 2.807 vs 6.356 ± 3.104, P = 0.290 and 0.493). L/G ratios of 13N-NH3 and 18F-FDOPA were significantly higher in TuR than in TrE group (13N-NH3, 1.573 ± 0.099 vs 1.025 ± 0.128, P = 0.008; 18F-FDOPA, 2.729 ± 0.131 vs 1.514 ± 0.141, P < 0.001). The sensitivity, specificity and AUC (area under the curve) by ROC (receiver operating characteristic) analysis were 57.7%, 100% and 0.803, for 13N-NH3; 84.6%, 100% and 0.938, for 18F-FDOPA; and 80.8%, 100%, and 0.952, for the combination, respectively. CONCLUSION: Our results suggest that although multiple tracer PET/CT may improve differential diagnosis efficacy, for glioma TuR from TrE, 18F-FDOPA PET-CT is the most reliable. The combination of 18F-FDOPA and 13N-NH3 does not increase the diagnostic efficiency, while 18F-FDG is not worthy for differential diagnosis of glioma TuR and TrE.

12.
Oncogene ; 40(26): 4453-4467, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34108621

RESUMO

Research over the past decade has suggested important roles for pseudogenes in glioma. This study aimed to show that pseudogene PRELI domain-containing 1 pseudogene 6 (PRELID1P6) promotes glioma progression. Aberrant expression of genes was screened using The Cancer Genome Atlas database. We found that mRNA level of PRELID1P6 was highly upregulated in glioma and was associated with a shorter survival time. Functional studies showed that the knockdown of PRELID1P6 decreased cell proliferation, sphere formation, and clone formation ability and blocked the cell cycle transition at G0/G1, while overexpression of PRELID1P6 had the opposite effects. Mechanistically, knockdown of PRELID1P6 changed the cellular localization of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) from nucleus to cytoplasm, which promoted ubiquitin-mediated degradation of hnRNPH1. RNA-sequence and gene set enrichment analysis suggested that knockdown of PRELID1P6 regulates the apoptosis signaling pathway. Western blotting showed that PRELID1P6 increased TRF2 expression by hnRNPH1-mediated alternative splicing effect and activated the Akt/mTOR pathway. Furthermore, Akt inhibitor MK2206 treatment reversed the oncogenic function of PRELID1P6. PRELID1P6 was also found to be negatively regulated by miR-1825. Our result showed that PRELID1P6 promotes glioma progression through the hnHNPH1-Akt/mTOR pathway. These findings shed new light on the important role of PRELID1P6 as a novel oncogene for glioma.

13.
Biomed Opt Express ; 12(4): 2508-2518, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33996244

RESUMO

Recent advancements in the high-speed long-range optical coherence tomography (OCT) endoscopy allow characterization of tissue compliance in the upper airway, an indicator of collapsibility. However, the resolution and accuracy of localized tissue compliance measurement are currently limited by the lack of a reliable nonuniform rotational distortion (NURD) correction method. In this study, we developed a robust 2-step NURD correction algorithm that can be applied to the dynamic OCT images obtained during the compliance measurement. We demonstrated the utility of the NURD correction algorithm by characterizing the local compliance of nasopharynx from an awake human subject for the first time.

14.
IEEE Trans Med Imaging ; 40(9): 2507-2512, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33999817

RESUMO

Optical coherence tomography (OCT) is a non-invasive diagnostic method that offers real-time visualization of the layered architecture of the skin in vivo. The 1.7-micron OCT system has been applied in cardiology, gynecology and dermatology, demonstrating an improved penetration depth in contrast to conventional 1.3-micron OCT. To further extend the capability, we developed a 1.7-micron OCT/OCT angiography (OCTA) system that allows for visualization of both morphology and microvasculature in the deeper layers of the skin. Using this imaging system, we imaged human skin with different benign lesions and described the corresponding features of both structure and vasculature. The significantly improved imaging depth and additional functional information suggest that the 1.7-micron OCTA system has great potential to advance both dermatological clinical and research settings for characterization of benign and cancerous skin lesions.


Assuntos
Dermatopatias , Tomografia de Coerência Óptica , Angiografia , Estudos de Viabilidade , Humanos , Pele/diagnóstico por imagem , Dermatopatias/diagnóstico por imagem
15.
J Control Release ; 334: 303-317, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-33933517

RESUMO

Bone metastasis is one of the leading causes of cancer-related death and remains incurable in spite of great efforts. Bone-targeted nanoparticle-based drug carriers can overcome the difficulties in delivering therapeutic agents to metastatic bone and endowing them with a stimuli-responsive feature for controllable drug release can further maximize their therapeutic outcome. In light of hypoxic microenvironment of bone metastasis, we herein reported a bone-targeted and hypoxia-responsive polymeric micelle system for effective treatment of bone metastatic prostate cancer. The micelles were self-assembled from a polyethylene glycol and poly-l-lysine based copolymer using alendronate as a bone-targeted moiety and azobenzene as a hypoxia-responsive linker, showing a high affinity to metastatic bone and a high sensitivity in responding to hypoxia in vitro. In vivo studies further showed that after a selective accumulation in metastatic bone, the micelles could respond to hypoxic bone metastasis for rapid drug release to an effective therapeutic dosage. As a result, the micelles could suppress tumor growth in bone and inhibit bone destruction by inhibiting osteoclast activity and promoting osteoblast activity, achieving an enhanced therapeutic outcome with relieved bone pain and prolonged survival time. Bone-targeted and hypoxia-responsive nanocarriers therefore represent a promising advancement for treating bone metastasis. To our best knowledge, it might be the first example of the application of hypoxia-responsive nanocarriers in treating bone metastasis.


Assuntos
Micelas , Neoplasias da Próstata , Alendronato , Linhagem Celular Tumoral , Portadores de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Hipóxia , Masculino , Polietilenoglicóis , Neoplasias da Próstata/tratamento farmacológico , Microambiente Tumoral
16.
Sci Rep ; 11(1): 9670, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958605

RESUMO

Numerous techniques have been demonstrated for effective generation of orbital angular momentum-carrying radiation, but intracavity generation of continuously tunable pulses in the femtosecond regime remains challenging. Even if such a creation was realized, the generated pulses-like all pulses in reality-are complex and transitory objects that can only be comprehensively characterized via multidimensional spaces. An integrated lasing system that generates pulses while simultaneously quantifies them can achieve adaptive pulse tailoring. Here, we report a femtosecond pulse scope that unifies vector vortex mode-locked lasing and vectorial quantification. With intracavity-controlled Pancharatnam-Berry phase modulation, continuous and ergodic generation of spirally polarized states along a broadband higher-order Poincaré sphere was realized. By intrinsically coupling a two-dimensional polarization-sensitive time-scanning interferometer to the laser, multidimensional spatiotemporal features of the pulse were further visualized. The proposed methodology paves the way for design optimization of ultrafast optics by integrating complex femtosecond pulse generation and structural customization, facilitating its applications in optical physics research and laser-based manufacturing.

17.
Front Cell Dev Biol ; 9: 653240, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796538

RESUMO

Background: Proteins containing the caspase recruitment domain (CARD) play critical roles in cell apoptosis and immunity. However, the impact of CARD genes in tumor immune cell infiltration, responsiveness to checkpoint immunotherapy, and clinical outcomes of gliomas remains unclear. Here, we explore using CARD genes to depict the immune microenvironment and predict the responsiveness of gliomas to anti-PD-1 therapy. Methods: The genome and transcriptome data of 231 patients with isocitrate dehydrogenase wild-type (IDH-wt) gliomas were retrieved from The Cancer Genome Atlas (TCGA) database to screen CARD genes associated with T lymphocyte infiltration in gliomas. Weighted co-expression network and LASSO penalized regression were employed to generate a CARD-associated risk score (CARS). Two independent and publicly available datasets were used to validate the effectiveness of CARS. Results: The CARS divided the 231 glioma patients into high- and low-risk subgroups with distinct immune microenvironment and molecular features. The high-risk group had high CARS and was characterized by enrichment of dysfunctional T lymphocytes in a profound immunosuppressive microenvironment, whereas the low-risk group had low CARS and exhibited an immune exclusion genotype. Moreover, signaling aberrations including upregulation of PI3K/Akt/mTOR, NF-κB, and TGF-ß were found in the high-risk group. In contrast, the activated WNT pathway was more evident in the low-risk group. Furthermore, we found that an elevated CARS indicated a decreased overall survival for IDH-wt gliomas under standard care but a clinical benefit from checkpoint immunotherapy. Conclusion: This study developed an immune- and prognosis-relevant risk score, which could be used to enhance our understanding of the heterogeneity of immune microenvironment of gliomas and facilitate to identify patients who will benefit from checkpoint immunotherapy.

18.
Front Cell Infect Microbiol ; 11: 646348, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816351

RESUMO

The pathogenesis of type 2 diabetes mellitus (T2DM) is commonly associated with altered gut bacteria. However, whether the microbial dysbiosis that exists in human diabetic patients with or without retinopathy is different remains largely unknown. Here, we collected clinical information and fecal samples from 75 participants, including 25 diabetic patients without retinopathy (DM), 25 diabetic patients with retinopathy (DR), and 25 healthy controls (HC). The gut microbial composition in the three groups was analyzed using 16S ribosomal RNA (rRNA) gene sequencing. Microbial structure and composition differed in the three groups. The α and ß diversities in both the DM and DR groups were reduced compared with those in the HC group. Blautia was the most abundant genus, especially in the DM group. In addition, increased levels of Bifidobacterium and Lactobacillus and decreased levels of Escherichia-Shigella, Faecalibacterium, Eubacterium_hallii_group and Clostridium genera were observed in the DM and DR groups compared with the HC group. Furthermore, a biomarker set of 25 bacterial families, which could distinguish patients in the DR group from those in the DM and HC groups was identified, with the area under the curve values ranging from 0.69 to 0.85. Of note, Pasteurellaceae, which was increased in DM and decreased in DR compared with HC, generated a high AUC (0.74) as an individual predictive biomarker. Moreover, 14 family biomarkers were associated with fasting blood glucose levels or diabetes, with most of them being negatively correlated. In summary, our study establishes compositional alterations of gut microbiota in DM and DR, suggesting the potential use of gut microbiota as a non-invasive biomarker for clinical and differential diagnosis, as well as identifying potential therapeutic targets of diabetic retinopathy.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Microbioma Gastrointestinal , Disbiose , Fezes , Humanos , RNA Ribossômico 16S
19.
Quant Imaging Med Surg ; 11(3): 918-927, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33654665

RESUMO

Background: Quantitatively investigating the biomechanics of retina with a retinal prosthetic electrode, we explored the effects of the prosthetic electrode on the retina, and further supplemented data for a potential clinical trial. Methods: Biomechanical properties were assessed with a high resolution optical coherence tomography (OCT) based elastography (OCE) system. A shaker was used to initiate elastic waves and an OCT system was used to track axial displacement along with wave propagation. Rabbits received surgery to implant the retinal prosthetic electrode, and elastic wave speed was measured before and after implantation; anatomical B-mode images were also acquired. Results: Spatial-temporal maps of each layer in retina with and without prosthetic electrodes were acquired. Elastic wave speed of nerve fiber to inner plexiform layer, inner nuclear to outer nuclear layer, retinal pigmented epithelium layer and choroid to sclera layer without prosthetic electrode were found to be 3.66±0.36, 5.33±0.07, 6.85±0.37, and 9.69±0.24 m/s, respectively. With prosthetic electrode, the elastic wave speed was found to be 4.09±0.26, 5.14±0.11, 6.88±0.70, and 9.99±0.73 m/s, respectively in each layer. Conclusions: Our results show that the elastic wave speed in each layer of retina is slightly faster with the retinal electrode, and further demonstrate that the retinal prosthetic electrode does not affect biomechanical properties significantly. In the future, we expect OCE technology to be used by clinicians where it could become part of routine testing and evaluation of the biomechanical properties of the retina in response to long term use of prosthetic electrodes in patients.

20.
Cancer Cell Int ; 21(1): 24, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407478

RESUMO

BACKGROUND: Glioblastoma multiforme, the most aggressive and malignant primary brain tumor, is characterized by rapid growth and extensive infiltration to neighboring normal brain parenchyma. Our previous studies delineated a crosstalk between PI3K/Akt and JNK signaling pathways, and a moderate anti-glioblastoma synergism caused by the combined inhibition of PI3K p110ß (PI3Kß) isoform and JNK. However, this combination strategy is not potent enough. MLK3, an upstream regulator of ERK and JNK, may replace JNK to exert stronger synergism with PI3Kß. METHODS: To develop a new combination strategy with stronger synergism, the expression pattern and roles of MLK3 in glioblastoma patient's specimens and cell lines were firstly investigated. Then glioblastoma cells and xenografts in nude mice were treated with the PI3Kß inhibitor AZD6482 and the MLK3 inhibitor URMC-099 alone or in combination to evaluate their combination effects on tumor cell growth and motility. The combination effects on cytoskeletal structures such as lamellipodia and focal adhesions were also evaluated. RESULTS: MLK3 protein was overexpressed in both newly diagnosed and relapsing glioblastoma patients' specimens. Silencing of MLK3 using siRNA duplexes significantly suppressed migration and invasion, but promoted attachment of glioblastoma cells. Combined inhibition of PI3Kß and MLK3 exhibited synergistic inhibitory effects on glioblastoma cell proliferation, migration and invasion, as well as the formation of lamellipodia and focal adhesions. Furthermore, combination of AZD6482 and URMC-099 effectively decreased glioblastoma xenograft growth in nude mice. Glioblastoma cells treated with this drug combination showed reduced phosphorylation of Akt and ERK, and decreased protein expression of ROCK2 and Zyxin. CONCLUSION: Taken together, combination of AZD6482 and URMC-099 showed strong synergistic anti-tumor effects on glioblastoma in vitro and in vivo. Our findings suggest that combined inhibition of PI3Kß and MLK3 may serve as an attractive therapeutic approach for glioblastoma multiforme.

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